| First Author | Fonseca MI | Year | 2004 |
| Journal | J Neurosci | Volume | 24 |
| Issue | 29 | Pages | 6457-65 |
| PubMed ID | 15269255 | Mgi Jnum | J:102186 |
| Mgi Id | MGI:3607035 | Doi | 10.1523/JNEUROSCI.0901-04.2004 |
| Citation | Fonseca MI, et al. (2004) Absence of C1q leads to less neuropathology in transgenic mouse models of Alzheimer's disease. J Neurosci 24(29):6457-65 |
| abstractText | C1q, the recognition component of the classical complement activation pathway, is a multifunctional protein known to be expressed in brain of Alzheimer's disease (AD) patients. To experimentally address the role of C1q in AD, a mouse model lacking C1q (APPQ-/-) was generated by crossing Tg2576 animals (APP) with C1q-deficient mice. The pathology of APPQ-/- was compared with that of APP mice and B6SJL controls at 3-16 months of age by immunohistochemistry and Western blot analysis. At younger ages (3-6 months), when no plaque pathology was present, no significant differences were seen in any of the neuronal or glial markers tested. At older ages (9-16 months), the APP and APPQ-/- mice developed comparable total amyloid and fibrillar beta-amyloid in frontal cortex and hippocampus; however, the level of activated glia surrounding the plaques was significantly lower in the APPQ-/- mice at 12 and 16 months. In addition, although Tg2576 mice showed a progressive decrease in synaptophysin and MAP2 in the CA3 area of hippocampus compared with control B6SJL at 9, 12, and 16 months, the APPQ-/- mice had significantly less of a decrease in these markers at 12 and 16 months. In a second murine model for AD containing transgenes for both APP and mutant presenilin 1 (APP/PS1), a similar reduction of pathology was seen in the APPPS1Q-/- mice. These data suggest that at ages when the fibrillar plaque pathology is present, C1q exerts a detrimental effect on neuronal integrity, most likely through the activation of the classical complement cascade and the enhancement of inflammation. |
